Conditional coupling of striatal dopamine D1 receptor to transcription factors: ontogenic and regional differences in CREB activation.

The coupling of striatal dopamine D1 receptors to c-fos transcription exhibit all-or-none regional and ontogenic differences: the D1 agonist SKF 38393 fails to induce c-fos expression in the striatum, except during the early postnatal period in the striosomes, or in the caudal extremity of the striatum in adult animals. In an attempt to better delineate the mechanism responsible for interrupting or enabling this conditional coupling of D1 receptors to c-fos transcription we have examined, through immunocytochemistry and gel shift assay, the activation of the cyclic AMP-response element binding protein (CREB) transcription factor in response to the D1 agonist in the murine striatum. Phosphorylated-CREB (P-CREB) immunoreactivity in response to the dopamine D1 agonist (+/-)SKF 38393 (15 mg/kg, i.p.) was prominent in the caudal extremity of the striatum in adult animals (P90). In neonatal (P5) mice, P-CREB immunoreactive neurons were observed both in the caudal and in the rostral parts of the striatum, without obvious patchy distribution. Gel shift assays performed on nuclear protein extracts from either the rostral or the caudal part of striatal tissue of neonatal (P5) or adult (P90) mice provided quantitative assessment, showing differences both in the amplitude and in the time course of the response, since P-CREB binding in adults culminated 45 min after (+/-)SKF 38393 (15 mg/kg, i.p.) injection, wheareas the peak value appeared as soon as 10 min after injection in P5 mouse pups, suggesting the involvement of partly distinct transduction pathways.